Direct exosome stimulation of peripheral humanT cells detected by ELISPOT

C Admyre, SM Johansson, S Paulie… - European journal of …, 2006 - Wiley Online Library
C Admyre, SM Johansson, S Paulie, S Gabrielsson
European journal of immunology, 2006Wiley Online Library
Exosomes from APC are nano‐vesicles that can induce antigen‐specific T cell responses
and are presently explored as therapeutic tools in different clinical settings. Investigations of
the capacity of exosomes to stimulate T cells in vitro have mostly been performed on T cell
hybridomas, clones or lines. Whether exosomes can stimulate T cells directly or need the
presence of dendritic cells (DC) is debated. We could detect exosome‐induced antigen‐
specific CD8+ T cell responses in peripheral blood from humans. Exosomes from monocyte …
Abstract
Exosomes from APC are nano‐vesicles that can induce antigen‐specific T cell responses and are presently explored as therapeutic tools in different clinical settings. Investigations of the capacity of exosomes to stimulate T cells in vitro have mostly been performed on T cell hybridomas, clones or lines. Whether exosomes can stimulate T cells directly or need the presence of dendritic cells (DC) is debated. We could detect exosome‐induced antigen‐specific CD8+ T cell responses in peripheral blood from humans. Exosomes from monocyte‐derived DC (MDDC) were loaded with a mix of 23 immunogenic peptides from EBV, CMV and influenza virus, and added to autologous peripheral CD8+ T cells. IFN‐γ‐producing cells were detected by enzyme‐linked immunospot assay (ELISPOT). MDDC‐exosomes induced IFN‐γ production in CD8+ T cells without addition of DC. The response was exosome dose dependent, and dependent on exosomal MHC class I. Furthermore, we detected an enhanced T cell stimulatory capacity by exosomes from lipopolysaccharide‐matured MDDC compared to exosomes from immature MDDC. Exosomes could also induce TNF‐α production. These results show, for the first time, that exosomes can directly stimulate human peripheral CD8+ T cells in an antigen‐specific manner and that ELISPOT is a suitable method for detecting exosome‐induced peripheral T cell responses. This system may provide a useful tool when developing exosomes as therapeutic agents.
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